Matching Items (33)
Description
Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristics of protons, resulting in superior healthy tissue sparing. This results in fewer unwanted side effects and improved outcomes for patients. Current available dosimeters are intrinsic, complex and expensive; hence cannot be used to determine the dose delivered to the tumor routinely. Here, we report a hydrogel based plasmonic nanosensor for measurements of clinical doses in ranges between 2-4 GyRBE. In this nanosensor, gold ions, encapsulated in a hydrogel, are reduced to gold nanoparticles following irradiation with proton beams. Formation of gold nanoparticles renders a color change to the originally colorless hydrogel. The intensity of the color can be used to calibrate the hydrogel nanosensor in order to quantify different radiation doses employed during treatment. The potential of this nanosensor for clinical translation was demonstrated using an anthropomorphic phantom mimicking a clinical radiotherapy session. The simplicity of fabrication, detection range in the fractionated radiotherapy regime and ease of detection with translational potential makes this a first-in-kind plasmonic colorimetric nanosensor for applications in clinical proton beam therapy.
ContributorsInamdar, Sahil (Author) / Rege, Kaushal (Thesis advisor) / Anand, Aman (Committee member) / Nannenga, Brent (Committee member) / Arizona State University (Publisher)
Created2017
Description
Lignocellulosic biomass represents a renewable domestic feedstock that can support large-scale biochemical production processes for fuels and specialty chemicals. However, cost-effective conversion of lignocellulosic sugars into valuable chemicals by microorganisms still remains a challenge. Biomass recalcitrance to saccharification, microbial substrate utilization, bioproduct titer toxicity, and toxic chemicals associated with chemical pretreatments are at the center of the bottlenecks limiting further commercialization of lignocellulose conversion. Genetic and metabolic engineering has allowed researchers to manipulate microorganisms to overcome some of these challenges, but new innovative approaches are needed to make the process more commercially viable. Transport proteins represent an underexplored target in genetic engineering that can potentially help to control the input of lignocellulosic substrate and output of products/toxins in microbial biocatalysts. In this work, I characterize and explore the use of transport systems to increase substrate utilization, conserve energy, increase tolerance, and enhance biocatalyst performance.
ContributorsKurgan, Gavin (Author) / Wang, Xuan (Thesis advisor) / Nielsen, David (Committee member) / Misra, Rajeev (Committee member) / Nannenga, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Description
Alzheimer’s disease is a major problem affecting over 5.7 million Americans. Although much is known about the effects of this neurogenerative disease, the exact pathogenesis is still unknown. One very important characteristic of Alzheimer’s is the accumulation of beta amyloid protein which often results in plaques. To understand these beta amyloid proteins better, antibody fragments may be used to bind to these oligomers and potentially reduce the effects of Alzheimer’s disease.
This thesis focused on the expression and crystallization the fragment antigen binding antibody fragment A4. A fragment antigen binding fragment was chosen to be worked with as it is more stable than many other antibody fragments. A4 is important in Alzheimer’s disease as it is able to identify toxic beta amyloid.
This thesis focused on the expression and crystallization the fragment antigen binding antibody fragment A4. A fragment antigen binding fragment was chosen to be worked with as it is more stable than many other antibody fragments. A4 is important in Alzheimer’s disease as it is able to identify toxic beta amyloid.
ContributorsColasurd, Paige (Author) / Nannenga, Brent (Thesis advisor) / Mills, Jeremy (Committee member) / Varman, Arul (Committee member) / Arizona State University (Publisher)
Created2018
Description
In the United States, 12% of women are typically diagnosed with breast cancer, where 20-30% of these cases are identified as Triple Negative Breast Cancer (TNBC). In the state of Arizona, 810 deaths occur due to breast cancer and more than 4,600 cases are diagnosed every year (American Cancer Society). The lack of estrogen, progesterone, and HER2 receptors in TNBC makes discovery of targeted therapies further challenging. To tackle this issue, a novel multi-component drug vehicle is presented. Previously, we have shown that mitoxantrone, a DNA damaging drug, can sensitize TNBC cells to TRAIL, which is a protein that can selectively kill cancer cells. In this current study, we have formulated aminoglycoside-derived nanoparticles (liposomes) loaded with mitoxantrone, PARP inhibitors, for delivery to cancer cells. PARP inhibitors are helpful in preventing cancer cells from repairing their DNA following damage with other drugs (e.g. mitoxantrone). Various treatment liposome groups, consisting of lipid-containing polymers (lipopolymers) synthesized in our laboratory, were formulated and characterized for their size, surface charge, and stability. PARP inhibitors and treatment of cells for in-vitro and in-vivo experiments with these liposomes resulted in synergistic death of cancer cells. Finally, studies to evaluate the pre-clinical efficacy of these approaches using immuno-deficient mouse models of TNBC disease have been initiated.
ContributorsMuralikrishnan, Harini (Author) / Rege, Kaushal (Thesis advisor) / Holechek, Susan (Committee member) / Nannenga, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Description
Rapid development of new technology has significantly disrupted the way radiotherapy is planned and delivered. These processes involve delivering high radiation doses to the target tumor while minimizing dose to the surrounding healthy tissue. However, with rapid implementation of these new technologies, there is a need for the detection of prescribed ionizing radiation for radioprotection of the patient and quality assurance of the technique employed. Most available clinical sensors are subjected to various limitations including requirement of extensive training, loss of readout with sequential measurements, sensitivity to light and post-irradiation wait time prior to analysis. Considering these disadvantages, there is still a need for a sensor that can be fabricated with ease and still operate effectively in predicting the delivered radiation dose.
The dissertation discusses the development of a sensor that changes color upon exposure to therapeutic levels of ionizing radiation used during routine radiotherapy. The underlying principle behind the sensor is based on the formation of gold nanoparticles from its colorless precursor salt solution upon exposure to ionizing radiation. Exposure to ionizing radiation generates free radicals which reduce ionic gold to its zerovalent gold form which further nucleate and mature into nanoparticles. The generation of these nanoparticles render a change in color from colorless to a maroon/pink depending on the intensity of incident ionizing radiation. The shade and the intensity of the color developed is used to quantitatively and qualitatively predict the prescribed radiation dose.
The dissertation further describes the applicability of sensor to detect a wide range of ionizing radiation including high energy photons, protons, electrons and emissions from radioactive isotopes while remaining insensitive to non-ionizing radiation. The sensor was further augmented with a capability to differentiate regions that are irradiated and non-irradiated in two dimensions. The dissertation further describes the ability of the sensor to predict dose deposition in all three dimensions. The efficacy of the sensor to predict the prescribed dose delivered to canine patients undergoing radiotherapy was also demonstrated. All these taken together demonstrate the potential of this technology to be translatable to the clinic to ensure patient safety during routine radiotherapy.
The dissertation discusses the development of a sensor that changes color upon exposure to therapeutic levels of ionizing radiation used during routine radiotherapy. The underlying principle behind the sensor is based on the formation of gold nanoparticles from its colorless precursor salt solution upon exposure to ionizing radiation. Exposure to ionizing radiation generates free radicals which reduce ionic gold to its zerovalent gold form which further nucleate and mature into nanoparticles. The generation of these nanoparticles render a change in color from colorless to a maroon/pink depending on the intensity of incident ionizing radiation. The shade and the intensity of the color developed is used to quantitatively and qualitatively predict the prescribed radiation dose.
The dissertation further describes the applicability of sensor to detect a wide range of ionizing radiation including high energy photons, protons, electrons and emissions from radioactive isotopes while remaining insensitive to non-ionizing radiation. The sensor was further augmented with a capability to differentiate regions that are irradiated and non-irradiated in two dimensions. The dissertation further describes the ability of the sensor to predict dose deposition in all three dimensions. The efficacy of the sensor to predict the prescribed dose delivered to canine patients undergoing radiotherapy was also demonstrated. All these taken together demonstrate the potential of this technology to be translatable to the clinic to ensure patient safety during routine radiotherapy.
ContributorsSubramaniam Pushpavanam, Karthik (Author) / Rege, Kaushal (Thesis advisor) / Sapareto, Stephen (Committee member) / Nannenga, Brent (Committee member) / Green, Matthew (Committee member) / Mu, Bin (Committee member) / Arizona State University (Publisher)
Created2019
Description
The primary objective of this project is to further the knowledge about SCL26 family of anion transporters. The goals of the experiment were to find the lowest sulfate concentration where the yeast without Sulp1 and Sulp2 is able to grow, but it grows very slowly, and to find a higher sulfate concentration where the yeast grows quickly, with or without the sulfate transporters. The lowest sulfate concentration where the yeast without the sulfate transporters is able to grow was determined to be 2-4 mM, however, this range can likely be refined by more quantitative analytical methods. At a sulfate concentration of 20 mM sulfate or higher, the yeast is able to grow quickly without high-affinity sulfate transporters. The next step in the project is to re-introduce the Sulp1 and Sulp2 genes into the yeast, so that growth in low and high sulfate conditions can be compared with and without the Sulp1 and Sulp2 proteins. The long-term goals of the project are to bring experience with yeast to Dr. Nannenga’s structural discovery lab, to determine if yeast sulfate transporters respond in the same way to drug candidates as human sulfate transporters, and to determine the structure of the proteins using cryo-electron microscopy.
ContributorsCall, Nicolas I (Author) / Nannenga, Brent (Thesis director) / Wang, Xuan (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Membrane proteins (MPs) are an important aspect of cell survival that ensure structural integrity, signaling, and transportation of molecules. Since 2015, over 450 MPs have been studied to find their functionalities and structure. Sufficient amounts of correctly folded MPs are needed to accurately study them through crystallography and other structural study methods. Use of recombinant technology is needed to overexpress MPs as natural abundance of MP is often too slow to provide the necessary amounts. However, an increase in toxicity and decrease in generation time deter the overexpression of MPs. The following report discusses two methods of enhancing overexpression in Escherchia coli, the use of T7 RNA polymerase (T7RNAP) and the reprogramming of chaperon pathways, that combats toxicity and promotes cell growth. Overall, both methods are proven to work effectively to overexpress MPs by regulating transcription rate of mRNA (T7RNAP) or folding and transporting of polypeptides to inner membrane (chaperon pathway). To further study the effectiveness of the two methods, they will need to be compared at the same conditions. In addition, a combination of two methods should also be studied to find out if the combination would have a great impact on the overexpression of the MPs.
ContributorsHan, Sue Jisue (Author) / Nannenga, Brent (Thesis director) / Green, Matthew (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Understanding the Current State of Vaccination Coverage in Arizona Schools: A Correlational Analysis
Description
The purpose of this study was to investigate what correlations exist between the immunization and personal belief exemption (PBE) rates and selected characteristics of Arizona schools. The demographic information of a school's student body, the percentage of student who are on free or reduced lunch, the presence of a Title I program at the school, the median household income of the zip code the school resides in, and the presence of a school nurse were all compared with immunization and PBE rates. Using data provided by the Arizona Department of Health Services (AZDHS), the National Center for Education Statistics (NCES), and the United States Census Bureau, these factors were investigated for kindergarten and 6th grade students. It was found that a higher percentage of white students in a student body was correlated with an higher rate of PBE and a lower immunization rate for measles, mumps, and rubella (MMR), polio, and hepatitis B. A higher percentage of Hispanic students in a student body was correlated with a lower rate of PBE and a higher immunization rate for measles, mumps, rubella (MMR), polio, and hepatitis B. There was little to no correlation between the percentage of students on free or reduced lunch and immunization or PBE rates. A higher median household income was correlated with a higher rate of PBE in public and private schools. Additionally, the immunization rates at schools with a nurse were significantly higher and the rate of PBE was significantly lower than at schools without a nurse. Finally, schools with a Title I program had mean immunization rates that were significantly higher and a mean PBE rate that was significantly lower than schools that did not have a Title I program.
ContributorsSellers, Abigail Leigh (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor) / Sandra Day O'Connor College of Law (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
With the new independence of adulthood, college students are a group susceptible to adopting unsupported, if not harmful, health practices. A survey of Arizona State University undergraduate students (N=200) was conducted to evaluate supplement use, trust in information sources, and beliefs about supplement regulation. Of those who reported using supplements, college students most frequently received information from friends and family. STEM majors in fields unrelated to health who were taking a supplement were found to be less likely to receive information about the supplement from a medical practitioner than those in health fields or those in non-STEM majors (-26.9%, p=0.018). STEM majors in health-related fields were 15.0% more likely to treat colds and/or cold symptoms with research-supported methods identified from reliable sources, while non-health STEM and non-STEM majors were more likely to take unsupported cold treatments (p=0.010). Surveyed students, regardless of major, also stated they would trust a medical practitioner for supplement advice above other sources (88.0%), and the majority expressed a belief that dietary supplements are approved/regulated by the government (59.8%).
ContributorsPerez, Jacob Tanner (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Continuing work has been done on a novel class of anti-cancer drugs employing a vinylogous extended amidine system functionalized into benzimidazole ring. Three new derivatives, utilizing a true sugar mimic at the N1-position, have been synthesized. Compounds 6-amino-1-[2-(2-hydroxyethoxy)ethyl-4-imino-2,5-dimethyl-1H-benzimidazole- 7-one (5), 6-amino-1-[2-(2-hydroxysulfonoethoxy)ethyl-4-imino-2,5-dimethyl-1H-benzimidazole-7-one (6), and 6-amino-1-[2-(2-hydroxysulfonoethoxy)ethyl-4-methylimino-2,5-dimethyl-1H-benzimidazole-7-one (7) have been synthesized utilizing similar protocols used in the synthesis of previously screened anti-tumor drugs produced by this laboratory. Compounds (5) and (6) have undergone screening similar to the National Cancer Institute’s (NCIs) Developmental Therapeutic Program (DTP), performed by Dr. Dan LaBarbera at the University of Boston. Both compounds show high cytotoxicity, with complete cell death at 5 µM and bioactive concentrations in the low nanomolar concentrations; more complete data is forthcoming. The proposed mechanism of action is through inhibition of p90RSK 1-2 which is responsible for the phosphorylation of Bcl-2 associated death promoter (BAD), a key metabolite in directing the onset of apoptosis. Future directions of next generation derivatives include modifying the 2-position of the benzimidazole ring into a halogenating or alkylating agent and possibly replacing the methanesulfonate with a phosphate group. This research is being published in the Journal of Medicinal Chemistry.
ContributorsMorrison, Zachary Tyler (Author) / Skibo, Edward (Thesis director) / Lefler, Scott (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05